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Temozolomide (Synonyms: CCRG 81045, MB 39831, Methazolastone, NSC 362856, Temodal, TMZ)

カタログ番号GC13667

テモゾロミドは、DNA内のO6-メチルグアニンの形成を誘導する経口活性アルキル化剤です。

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Temozolomide 化学構造

Cas No.: 85622-93-1

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10mM (in 1mL DMSO)
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100mg
$55.00
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10mg
$28.00
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200mg
$66.00
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50mg
$45.00
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1g
$105.00
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500mg
$87.00
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2g
$290.00
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5g
$550.00
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Sample solution is provided at 25 µL, 10mM.

Product has been cited by 1 publications

Product Documents

Quality Control & SDS

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Protocol

Cell experiment [1]:

Cell lines

U-118 GBM cell line

Preparation Method

Cells were subcultured every 48 h by lifting them up with a cell scrapper. The cells were then centrifuged and resuspended in fresh DMEM. For the experiments, unsynchronized cells were treated with different concentrations of Temozolomide (0, 10, 20, 100, 250 and 500 µM) for 24 and 48 h. Assays were previously performed in the presence of DMSO, which corresponded to each Temozolomide concentration.

Reaction Conditions

0, 10, 20, 100, 250 and 500 µM for 24 and 48 h

Applications

The effect of Temozolomide was particularly evident when U-118 cells were incubated with Temozolomide concentrations of >100 µM. When U-118 cells were incubated with Temozolomide (250 µM) the proliferation rate was inhibited by 43.2%, as compared to that observed in the control cells.

Animal experiment [2]:

Animal models

Male B6D2F1 (C57BL/6 × DBA/2) mice

Preparation Method

L5178Y cells (104 in 0.03 mL RPMI-1640) were then injected intracranially, through the center-middle area of the frontal bone to a 2-mm depth, using a 0.1-mL glass microsyringe and a 27-gauge disposable needle. Temozolomide was dissolved in dimethyl-sulfoxide (40 mg/mL), diluted in saline (5 mg/mL), and administered intraperitoneally on day 2 after tumor injection at 100 mg/kg or 200 mg/kg, total dose of 200 mg/kg Temozolomide was divided in 2 doses of 100 mg/kg given on days 2 and 3.

Dosage form

Intraperitoneal injection, 100, 200 mg/kg

Applications

Intracranial injection of NU1025, immediately before the administration of 100 or 200 mg/kg Temozolomide, significantly increased lifespans with respect to controls or to groups treated with Temozolomide only. When Temozolomide was fractionated, the ILS obtained with this schedule was higher than that observed when NU1025 was combined with a single injection of Temozolomide.

References:

[1]: Carmo A, Carvalheiro H, Crespo I, et al. Effect of Temozolomide on the U-118 glioma cell line[J]. Oncology letters, 2011, 2(6): 1165-1170.
[2]: Tentori L, Leonetti C, Scarsella M, et al. Combined treatment with Temozolomide and poly (ADP-ribose) polymerase inhibitor enhances survival of mice bearing hematologic malignancy at the central nervous system site[J]. Blood, The Journal of the American Society of Hematology, 2002, 99(6): 2241-2244.

Background

テモゾロミドは、DNA中のO6-メチルグアニンの形成を誘導し、次のDNA複製周期中にチミンと誤対合する口服用アルキル化剤であり、アポトーシス経路を活性化します。テモゾロミドは血液脳関門を通過し、悪性グリオーマや転移性黒色腫に適応があります[1]。テモゾロミドはG2/M期で細胞周期停止を引き起こし、最終的にアポトーシスへと導くことが示されています[2]。生理学的pHでは、短命な有効成分MTICに変換されます。MTICはさらに5-アミノイミダゾール-4-カルボキサマイド(AIC)およびメチル水素酸に加水分解されます。テモゾロミドの細胞毒性は、genomic DNA上のグアニンのN7およびO6サイトおよびアデニンのO3サイトにメチル基を付加することで媒介されます。グアニン上のO6サイトのアルキレーションは、後続するDNA複製時にメチルグアニンの代わりにシトシンが挿入され、これが細胞死を引き起こす可能性があります[3]。

治療後72時間に行われたリンパ腫細胞のカウントでは、Temozolomideを単独で使用した場合のIC50は44 µM(35-58 µM)であり、NU1025と併用した場合は16 µM(12-26 µM)であったことが示されました[1]。U251MGグリオブラストーマ細胞においては、Temozolomide(100µM)を単独で処理した際にDNA鎖切断形成の時間依存性反応が観察されました[4]。特にU-118細胞がTemozolomide濃度>100µMで培養された場合、その効果が顕著であることが明らかになりました。U-118細胞をTemozolomide(250µM)で培養した場合、増殖率は43.2%抑制されました[5]

テモゾロミドは、一貫して再現性のある線形薬物動態を示し、約100%の経口生体利用度があります[6]。初期段階のs.c. SNB-75アストロサイトーマモデルでは、5日目に投与された400 mg/kgのテモゾロミド投与で10匹中10匹が54日目まで腫瘍フリーとなりました。後期段階のs.c. U251およびSF-295グリオブラストーマモデルでは、単回600 mg/kg投与でそれぞれ10匹中9匹(86日目)および2匹中1匹(40日目)が腫瘍フリーとなりました。後者のグループでは315%以上の腫瘍成長遅延が得られました[7]。CEP 6800(30 mg/kg)をテモゾロミド(17および34 mg/kg)と併用することにより、U251MG腫瘍100%完全寛解率を28日以内に達成しました。これは、単独でテモゾロミドを使用した場合に引き起こされる60%完全寛解率よりも高いです[4]。

References:
[1]. Tentori L, Leonetti C, Scarsella M, et al. Combined treatment with temozolomide and poly (ADP-ribose) polymerase inhibitor enhances survival of mice bearing hematologic malignancy at the central nervous system site[J]. Blood, The Journal of the American Society of Hematology, 2002, 99(6): 2241-2244.
[2]. Baer J C, Freeman A A, Newlands E S, et al. Depletion of O6-alkylguanine-DNA alkyltransferase correlates with potentiation of temozolomide and CCNU toxicity in human tumour cells[J]. British journal of cancer, 1993, 67(6): 1299-1302.
[3]. Lee S Y. Temozolomide resistance in glioblastoma multiforme[J]. Genes & diseases, 2016, 3(3): 198-210.
[4]. Miknyoczki S J, Jones-Bolin S, Pritchard S, et al. Chemopotentiation of temozolomide, irinotecan, and cisplatin activity by CEP-6800, a poly (ADP-ribose) polymerase inhibitor[J]. Molecular cancer therapeutics, 2003, 2(4): 371-382.
[5]. Carmo A, Carvalheiro H, Crespo I, et al. Effect of temozolomide on the U-118 glioma cell line[J]. Oncology letters, 2011, 2(6): 1165-1170.
[6]. Friedman H S, Kerby T, Calvert H. Temozolomide and treatment of malignant glioma[J]. Clinical cancer research, 2000, 6(7): 2585-2597.
[7]. Plowman J, Waud W R, Koutsoukos A D, et al. Preclinical antitumor activity of temozolomide in mice: efficacy against human brain tumor xenografts and synergism with 1, 3-bis (2-chloroethyl)-1-nitrosourea[J]. Cancer research, 1994, 54(14): 3793-3799.

Chemical Properties

Cas No. 85622-93-1 SDF
同義語 CCRG 81045, MB 39831, Methazolastone, NSC 362856, Temodal, TMZ
Chemical Name 3-methyl-4-oxoimidazo[5,1-d][1,2,3,5]tetrazine-8-carboxamide
Canonical SMILES CN1C(=O)N2C=NC(=C2N=N1)C(=O)N
Formula C6H6N6O2 M.Wt 194.15
溶解度 ≥ 29.61mg/mL in DMSO Storage Store at -20°C, protect from light, stored under nitrogen
General tips Please select the appropriate solvent to prepare the stock solution according to the solubility of the product in different solvents; once the solution is prepared, please store it in separate packages to avoid product failure caused by repeated freezing and thawing.Storage method and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored at -20°C, please use it within 1 month.
To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time.
Shipping Condition Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request.

Complete Stock Solution Preparation Table

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1 mg 5 mg 10 mg
1 mM 5.1507 mL 25.7533 mL 51.5066 mL
5 mM 1.0301 mL 5.1507 mL 10.3013 mL
10 mM 0.5151 mL 2.5753 mL 5.1507 mL
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Average Rating: 5 ★★★★★ (Based on Reviews and 8 reference(s) in Google Scholar.)

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